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  • 1
    Language: English
    In: Histochemistry and Cell Biology, 2017, Vol.147(2), pp.175-198
    Description: Glycolipids are glycoconjugates that are predominantly found on the extracellular surface of cells ranging from bacteria to men. In bacteria and plants, glycoglycerolipids represent the main glycolipid species. Ceramides as carrier for glycans, termed glycosphingolipids (GSLs), are characteristic for vertebrates and insects. The glycan part is involved in a variety of biological activities including cell adhesion and initiation of signaling. Most of these functions rest on two basic principles: (1) GSLs spontaneously contribute to organize lipid rafts in biological membranes, thereby forming functional complexes (‘glycosynapses’) with receptor proteins and ion channels and (2) their glycans are bound by receptors like galectins (protein–glycan recognition) or cognate glycans (glycan–glycan recognition). This interaction modulates cell adhesion, differentiation and growth processes. Besides their contribution to normal cell behavior, GSL expression patterns also influence disease processes by inducing cellular malfunctions when aberrant, as highlighted by inherited disorders of GSL metabolism like sphingolipidoses. Altered GSL patterns are also associated with common neurological diseases, autoimmune diseases and cancer. With respect to infections, various GSL-presented glycans are attachment sites for bacteria and viruses as well as primary targets for bacterial toxins. This review provides an introduction to GSL structures, their nomenclature and metabolism. Building on this, normal and pathological functions of GSL will be surveyed.
    Keywords: Ganglioside ; Glycosphingolipid ; Lectin ; Lipid raft ; Neuroblastoma
    ISSN: 0948-6143
    E-ISSN: 1432-119X
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  • 2
    Language: English
    In: Cancer Research, 08/01/2015, Vol.75(15 Supplement), pp.1070-1070
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
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  • 3
    Language: English
    In: Cancer Research, 04/15/2012, Vol.72(8 Supplement), pp.1085-1085
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
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  • 4
    Language: English
    In: Neuroscience Letters, 07 February 2014, Vol.560, pp.117-121
    Description: Levosimendan shows protective myocardial characteristics and is administered to enhance cardiac contractility in patients. However, currently little is known about levosimendan's effect on brain. The aim of this pilot study was to investigate the long-term effect of levosimendan on brain and during mild rat sepsis in comparison to its peripheral mode of action. Adult rats ( = 40) were divided into four groups with = 10 per group: (I) sham, (II) levosimendan (283 μg/kg body weight i.v.), (III) lipopolysaccharide (LPS, 8 mg/kg body weight i.p.), and (IV) LPS+levosimendan. Levosimendan was given 24 h after injecting LPS. Psychometric investigations were conducted using a Morris water maze (MWM) and a holeboard test. In cerebral and splenic tissue, IL-1β, Il-6, TNFalpha levels, and apoptosis were determined; cerebral tissue corticosterone concentration was measured 6 days after injecting LPS. Blood cytokine concentrations were determined 1 day and 6 days after injecting LPS. Rats that received an LPS injection spent more time in the outer zone of the MWM according to increased cerebral corticosterone levels, and showed decreased cognitive abilities. LPS induced a reduction in body weight, increased splenic apoptosis and blood cytokine level. Levosimendan showed anti-inflammatory and anti-apoptotic properties in spleen but failed to show a long-term neuroprotective effect.
    Keywords: Levosimendan ; Neuroprotection ; Cognition ; Inflammation ; Lps ; Endotoxinemia ; Medicine ; Anatomy & Physiology
    ISSN: 0304-3940
    E-ISSN: 1872-7972
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  • 5
    In: PLoS ONE, 2013, Vol.8(2)
    Description: Aberrant glycosylation is a common feature of many malignancies including colorectal cancers (CRCs). About 15% of CRC show the microsatellite instability (MSI) phenotype that is associated with a high frequency of biallelic frameshift mutations in the A10 coding mononucleotide microsatellite of the transforming growth factor beta receptor 2 ( TGFBR2 ) gene. If and how impaired TGFBR2 signaling in MSI CRC cells affects cell surface glycan pattern is largely unexplored. Here, we used the TGFBR2-deficient MSI colon carcinoma cell line HCT116 as a model system. Stable clones conferring doxycycline (dox)-inducible expression of a single copy wildtype TGFBR2 transgene were generated by recombinase-mediated cassette exchange (RMCE). In two independent clones, dox-inducible expression of wildtype TGFBR2 protein and reconstitution of its signaling function was shown. Metabolic labeling experiments using the tritiated sialic acid precursor N -acetyl-D-mannosamine (ManNAc) revealed a significant decline (∼30%) of its incorporation into newly synthesized sialoglycoproteins in a TGFBR2-dependent manner. In particular, we detected a significant decrease of sialylated ß1-integrin upon reconstituted TGFBR2 signaling which did not influence ß1-integrin protein turnover. Notably, TGFBR2 reconstitution did not affect the transcript levels of any of the known human sialyltransferases when examined by real-time RT- PCR analysis. These results suggest that reconstituted TGFBR2 signaling in an isogenic MSI cell line model system can modulate sialylation of cell surface proteins like ß1-integrin. Moreover, our model system will be suitable to uncover the underlying molecular mechanisms of altered MSI tumor glycobiology.
    Keywords: Research Article ; Biology
    E-ISSN: 1932-6203
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  • 6
    In: Annals of the New York Academy of Sciences, April 2012, Vol.12531(1), pp.206-221
    Description: Glycoprotein glycan chains, by virtue of structure, topology of presentation and connection to signal‐inducing units, are functional galectin counterreceptors. As example, cross‐linking of the αβ integrin by galectin‐1 on carcinoma cells leads to G arrest or anoikis. Contact‐dependent switching from proliferation to differentiation in cultured neuroblastoma cells (SK‐N‐MC) also utilizes galectin‐1. Activity enhancement of a cell surface sialidase underlies the shift in glycan display to ganglioside GM1. Its pentasaccharide within microdomains becomes the target. Similarly, this recognition pair is upregulated upon T cell activation. Cross‐linking of GM1 along with associated α/αβ integrins elicits Ca‐influx via TRPC5 channels as the relevant response for T effector cell (T) suppression. Unlike T cells from wild‐type mice, those from genetically altered mice lacking GM1 are not suppressed by galectin‐1 or regulatory T cells. Similarly, in the context of GM1 deficiency in NOD mice, T cells are associated with resistance to regulatory T cell suppression, which is reversed by applied GM1. The broad array of glycosphingolipid structures suggests the possible existence of several novel counterreceptors targeted to endogenous lectins, with sulfatide–galectin‐4 interplay within apical delivery serving as recent example.
    Keywords: Anoikis ; Carcinoma ; Diabetes ; Galectin‐1 ; Glycosphingolipid ; Gm1 Ganglioside ; Immune Suppression ; T Cells
    ISSN: 0077-8923
    E-ISSN: 1749-6632
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  • 7
    Language: English
    In: Journal of Pain and Symptom Management, October 2016, Vol.52(4), pp.525-532
    Description: Delirium is an important complication in palliative care patients. One of the potential risk factors for cognitive disorders is deterioration in cholinergic neurotransmission. Anticholinergic medications are known to be important owing to the association of their metabolites with significant morbidity, which is often the result of cumulative effects of medications (anticholinergic burden). Additionally, cholinergic enzymes are possible candidates reflecting the cholinergic situation in patients. However, the role of cholinesterases (CHE) for delirium in palliative care patients is unknown. Following local Ethics Board approval and written informed consent, we recruited a cohort of patients who had been admitted to the Heidelberg University Palliative Care Unit related to CHE and other factors at risk for delirium. Delirium was assessed using the Nursing Delirium Screening Scale once daily in all cancer patients (  = 100) during their stay on the palliative care unit. In a subgroup of 69 probes, blood samples were analyzed for acetyl- and butyrylcholinesterase activity spectrophotometrically. Furthermore, patients’ medications were recorded. Logistic regression analysis was used to evaluate potential predictors of delirium. Delirium was identified in 29% of patients. Karnofsky Performance Status Scale score was significantly lower (  = 0.021) and mortality higher (  = 0.018) in patients with delirium. Plasma CHE activity was not associated with delirium. However, a significant effect of anticholinergic medication on plasma CHE activity was detected; so far midazolam (  = 0.01) seems to play an important role in that process. Special care might be necessary with anticholinergic medication to minimize risk for delirium in palliative cancer patients.
    Keywords: Acetylcholinesterase ; Butyrylcholinesterase ; Delirium ; Palliative Care Patients ; Risk Factors ; Medicine
    ISSN: 0885-3924
    E-ISSN: 1873-6513
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  • 8
    Language: English
    In: Journal of Environmental Radioactivity, August, 2014, Vol.134, p.109(5)
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jenvrad.2014.03.005 Byline: Michael Schubert, Juergen Kopitz, StanisAaw ChaAupnik Abstract: Radon is used as environmental tracer in a wide range of applications particularly in aquatic environments. If liquid scintillation counting (LSC) is used as detection method the radon has to be transferred from the water sample into a scintillation cocktail. Whereas the volume of the cocktail is generally given by the size of standard LSC vials (20 ml) the water sample volume is not specified. Aim of the study was an optimization of the water sample volume, i.e. its minimization without risking a significant decrease in LSC count-rate and hence in counting statistics. An equation is introduced, which allows calculating the A[sup.2]A[sup.2]A[sup.2]Rn concentration that was initially present in a water sample as function of the volumes of water sample, sample flask headspace and scintillation cocktail, the applicable radon partition coefficient, and the detected count-rate value. It was shown that water sample volumes exceeding about 900 ml do not result in a significant increase in count-rate and hence counting statistics. On the other hand, sample volumes that are considerably smaller than about 500 ml lead to noticeably lower count-rates (and poorer counting statistics). Thus water sample volumes of about 500-900 ml should be chosen for LSC radon-in-water detection, if 20 ml vials are applied. Author Affiliation: (a) Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany (b) Universitatsklinikum Heidelberg, Im Neuenheimer Feld 672, 69120 Heidelberg, Germany (c) Silesian Centre for Environmental Radioactivity, Central Mining Institute, Pl. Gwarkow, 140-166 Katowice, Poland Article History: Received 27 November 2013; Revised 7 February 2014; Accepted 9 March 2014
    Keywords: Tracers (Chemistry) ; Water
    ISSN: 0265-931X
    Source: Cengage Learning, Inc.
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  • 9
    Language: English
    In: PLoS ONE, 01 January 2015, Vol.10(6), p.e0131506
    Description: Although inactivating frameshift mutations in the Transforming growth factor beta receptor type 2 (TGFBR2) gene are considered as drivers of microsatellite unstable (MSI) colorectal tumorigenesis, consequential alterations of the downstream target proteome are not resolved completely. Applying a click-it chemistry protein labeling approach combined with mass spectrometry in a MSI colorectal cancer model cell line, we identified 21 de novo synthesized proteins differentially expressed upon reconstituted TGFBR2 expression. One candidate gene, the TGF-ß family member Growth differentiation factor-15 (GDF-15), exhibited TGFBR2-dependent transcriptional upregulation causing increased intracellular and extracellular protein levels. As a new TGFBR2 target gene it may provide a link between the TGF-ß branch and the BMP/GDF branch of SMAD-mediated signaling.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 10
    Language: English
    In: Journal of Psychiatric Research, October 2012, Vol.46(10), pp.1339-1345
    Description: Delirium, a frequently occurring, devastating disease, is often underdiagnosed, especially in dementia. Serum anticholinergic activity (SAA) was proposed as a disease marker as it may reflect delirium's important pathogenetic mechanism, cholinergic deficiency. We assessed the association of serum anticholinergic activity with delirium and its risk factors in a longitudinal study on elderly hip fracture patients. Consecutive elderly patients admitted for hip fracture surgery (  = 142) were assessed longitudinally for delirium, risk factors, and serum markers (IL-6, cortisol, and SAA). Using a sophisticated statistical design, we evaluated the association between SAA and delirium in general and with adjustments, but also the temporal course, including the events fracture, surgery, and potential delirium, individual confounders, and a propensity score. Among elderly hip fracture patients 51% developed delirium, these showed more risk factors (  〈 0.001), and complications (  〈 0.05). Uncontrolled SAA levels (463 samples) were significantly higher in the delirium group (4.2 vs. 3.4 pmol/ml) and increased with delirium onset, but risk factors absorbed the effect. Using mixed-modeling we found a significant increase in SAA concentration (7.6% (95%CI 5.0–10.2,  〈 0.001)) per day, which was modified by surgery and delirium, but this effect was confounded by cognitive impairment and IL-6 values. Confounder control by propensity scores resulted in a disappearance of delirium-induced SAA increase. Delirium-predisposing factors are closely associated with changes in the temporal profile of serum anticholinergic activity and thus neutralize the previously documented association between higher SAA levels and delirium. An independent relationship of SAA to delirium presence is highly questionable.
    Keywords: Delirium ; Geriatrics ; Hip Fracture ; Anticholinergics ; Cognitive Impairment ; Dementia ; Old Age ; Biomarker ; Medicine
    ISSN: 0022-3956
    E-ISSN: 1879-1379
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